Drugs and the exercise test.
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Biomedical subjects
Publications and source records attributed to D S Dymond.
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During exercise radionuclide ventriculography, many patients with coronary artery disease exhibit painless myocardial ischemia defined as an abnormal left ventricular ejection fraction response without accompanying angina. To see if complete suppression of such exercise-induced painless ischemia by anti-ischemic medication implies a better prognosis in medically treated coronary artery disease, 34 patients underwent repeat testing at 4 weeks receiving regular conventional therapy that rendered angina no worse than class I. With such therapy, painless ischemia was abolished in 12 patients (group I) and persisted in 22 (65%, group II). Both groups were similar in age, number of diseased vessels, proportion with previous myocardial infarction, exercise ejection fraction, and degree of exercise-induced painless ischemia at baseline. At 9 months, adverse events had occurred in 11 patients (2 patients with myocardial infarction, 4 with unstable angina, 2 with angioplasty and 3 with bypass surgery). Only 1 of 12 patients (8%) in group I had experienced events compared with 10 of 22 (45%) in group II (chi-square, 5.4; p less than 0.025; 95% confidence interval, 12 to 61%). Thus, the relative risk of adverse events in patients whose painless ischemia was abolished was only 18% of that in patients in whom it was persistent. These results suggest that (1) the abolition of exercise-induced painless ischemia by conventional symptom-dictated medical therapy confers a better short-term prognosis in medically treated coronary artery disease, and (2) therapeutic efficacy may need to be assessed by titration against ischemia and not against angina.
Percutaneous transluminal coronary angioplasty was attempted with elective percutaneous intra-aortic balloon pump support in 21 patients (mean age 60 years, range 40-82; 18 males) with unstable angina (n = 2), multivessel coronary disease requiring multivessel angioplasty (n = 2), severe left ventricular dysfunction (ejection fraction 10-30%; n = 16) or ventricular fibrillation at diagnostic angiography (n = 1). Fourteen patients had 3-vessel disease (1 with vein grafts also diseased), 6 had 2-vessel disease and 1 had isolated left anterior descending disease. Twenty-five procedures were performed (one in 18 patients, two in 2 patients and three in one patient) on 42 lesions in 34 vessels/grafts. There was no angioplasty-related death. Successful dilatation was achieved in 38/42 lesions (90%) in 21/25 procedures (84%) without major complication. Three procedures were complicated: one by major coronary dissection without sequelae, one by haemodynamic deterioration due to distal occlusion and one by an unstable residual stenosis in the attempted vessel necessitating urgent bypass surgery. The only complication related to the intra-aortic balloon pump was local haematoma in 2 patients. In conclusion, elective intra-aortic balloon pump support may be safely used to stabilise high-risk patients undergoing coronary angioplasty, leading to a satisfactory primary success rate.
Most count-based radionuclide methods for calculating left ventricular volume rely on measurement of radioactivity in a peripheral blood sample and a measurement of ventricle to collimator distance. We have developed a method which requires neither a blood sample nor a distance measurement and which is applicable to first-pass radionuclide angiography. The parameters used to calculate volume are the area of pixel, the total counts in the left ventricle and the maximum pixel count. The equation was used to calculate the volumes in 50 patients who had both resting first-pass radionuclide angiography (25 patients with a single crystal and 25 patients with a multicrystal camera) and contrast ventriculography on the same day. Correlation coefficients for end-diastolic and end-systolic volumes showed r ranging 0.93-0.98 and standard error of estimate ranging 23-35 ml for end-diastolic volume (14%-17% of mean end-diastolic volume) and 16-23 ml for end-systolic volume (18%-21% of mean end-systolic volume). Image processing software for extracting the needed values is generally available on most commercial nuclear medicine imaging systems and the additional time for the calculations is short. Although the theory is based on multiple assumptions, the volume calculation appears to be reasonably accurate and clinically applicable.
We examined the prognostic value of exercise radionuclide ventriculography (RNV) performed on anti-ischaemic medication following thrombolysis. Within 3 months of thrombolysis for first myocardial infarction, 31 medically treated patients with revascularisable but non-critical and minimally symptomatic coronary disease had left ventricular ejection fraction (LVEF) measured by first-pass exercise RNV. This was first performed off treatment and then repeated within 4 weeks on patients' regular medication. Follow-up at 12 months post-thrombolysis showed that 5 patients (Group I) had suffered significant recurrent symptoms (worsening angina requiring revascularisation in 3, unstable angina in 1, reinfarction in 1), but 26 remained well (Group II). Both groups were similar in age, post-thrombolytic severity of coronary disease, exercise LVEF whether off (39% vs 43%) or on medication (43% vs 44%), and change in LVEF with exercise ([symbol: see text]LVEF) off medication (-11% vs - 3%). However, on medication, there was a significant difference in mean [symbol: see text]LVEF between Groups I and II (-11% vs + 5%, P = 0.0008, 99% confidence interval = 4 to 26%). Thus, following thrombolysis, an abnormal [symbol: see text]LVEF despite anti-ischaemic medication may identify patients at risk of significant early recurrent ischaemia. Post-thrombolysis prognostic testing by exercise RNV may therefore be of greater value when performed on rather than off medication.
Twenty one patients with NYHA class II-III congestive heart failure received single ascending doses of 0.5, 1.25 and 2.5 mg cilazapril daily followed by the minimum effective dose for six weeks. Fifteen patients completed the study, but the data from only 11 were sufficiently complete for kinetic evaluation. The pharmacokinetics of the metabolite, cilazaprilat, after a single dose of 0.5 mg cilazapril were similar to previous observations in healthy volunteers at identical dosage. Repeat administration, however, led to greater accumulation than previously observed in volunteers at the higher dosages of 1.25 or 5 mg given for 8 days. Seven patients experienced adverse events. Four were severe, leading to withdrawal of the patients from the study, but only one event was related to cilazapril. Of the other three, one suffered a myocardial infarction and subsequently died due to worsening congestive heart failure. One other patient was withdrawn with two adverse events probably related to cilazapril. No other deaths occurred amongst the study population, and there were no significant abnormalities in haematology or blood chemistry.
We examined retrospectively the usefulness of routine clinic visits in preventing adverse cardiac events in 115 patients awaiting coronary surgery or angioplasty. Mean waiting time from angiography to revascularization was 126 days. A total of 126 visits were made by 80 patients. No deaths occurred, but one patient, despite three visits, suffered myocardial infarction at 316 days post-angiography. Eight patients required admission for unstable angina, five having been on the waiting list for less than 5 weeks. The mean number of clinic visits, number of diseased vessels and proportion on triple anti-ischaemic therapy were similar in the patients suffering such events and those remaining stable. In conclusion, the inherent unpredictability of coronary disease greatly limits the role of interim clinic visits in the prevention of adverse cardiac events in patients awaiting revascularization.
We conducted a retrospective study to correlate thrombotic variables with the risk from an acute coronary event, using a new in vitro technique, which measures haemostasis, thrombolysis and coagulation from non-anticoagulated blood samples. The analysis was based on data from 63 patients who had undergone exercise radionuclide ventriculography, 50 of whom were considered to be at risk from an acute coronary event because they satisfied at least one of the following three criteria: (1) coronary angiography documented disease, (2) prior myocardial infarction, (3) ventriculography assessed provocable ischaemia. Fifty matched normal subjects were used as controls. Significantly enhanced haemostasis was measured in patients considered at risk from acute coronary event, and haemostatic activity was further increased in patients with provocable ischaemia. Haemostasis in eight patients at risk (provocable ischaemia), who continued with the medication during the test, did not differ significantly from the controls. Greatly reduced spontaneous thrombolytic activity was measured in all patients at risk from acute coronary events. These findings suggest the presence of hyperactive platelets in patients at risk from acute coronary events, with an additional risk of greatly reduced spontaneous thrombolytic activity.
It is very important to pay attention to technical detail when acquiring nuclear scans of the heart. It must be remembered that not only is the heart a three dimensional structure, which imposes its own limitations on the interpretation of information represented as two dimensional images, but the organ also moves which will in turn degrade static images. Dynamic studies of left ventricular function must be able to resolve the rapidly changing events of the cardiac cycle which makes specific technical demands upon the imaging equipment and computer system used. In spite of these potential drawbacks, both static and dynamic imaging of the heart using radiopharmaceuticals are widely used in a clinical and research environment. In this article some of the technical considerations will be covered as they apply to both the commonly used clinical applications of nuclear cardiology and some of the newer but potentially exciting techniques will also be covered briefly.
This paper describes how the clinical applications of radionuclide ventriculography have developed during the last decade. The role of resting radionuclide angiography in the assessment of myocardial infarctions, suspected left ventricular aneurysms, and the assessment of right ventricular function are discussed. Currently exercise radionuclide angiography probably represents the best way of assessing left ventricular function under stress. Extensive experience has been gained with this technique in a large number of centres worldwide. Initially the techniques were compared against coronary arteriography as the gold standard, figures for sensitivity, specificity and predictive value of the test in predicting stenosed coronary arteries were produced. This article points out that the exercise study demonstrates the physiological response of the left ventricle to exercise and not every patient with coronary artery disease can be expected to manifest abnormal physiology. Certain valuable prognostic information may be obtained from the results of the exercise radionuclide studies which may guide cardiologists as to which patients should be treated conservatively and which patients should undergo a prognostic intervention. The techniques are of major value in determining the results of both medical and interventional therapy. Abnormal ventricular function response to exercise is not specific for coronary artery disease however, and the relevance of the study must be analysed in relationship to the population under investigation.
St Bartholomew's Hospital, in the City of London, has for many years run a Coronary Ambulance service, called by the public via the 999 system. During a 9-month period only 55% of 214 cardiac emergencies arriving at St Bartholomew's Hospital came with Coronary Ambulance support, although the service was available if called. In cases where the Coronary Ambulance was summoned, the call-out was inappropriate in 57% of cases. In addition, 153 cardiac emergencies arrived at the Accident and Emergency Department during hours when the Coronary Ambulance was not available. Reasons for breakdowns in the call-out system are discussed and remedies involving the public and London Ambulance Control are suggested.
Respiratory effort during inspiration, expiration, and the Valsalva manoeuvre changes right ventricular preload and afterload. On inspiration these changes should improve systolic emptying of a larger end diastolic volume and so increase the ejection fraction, whereas on expiration the reverse should be true. The resting right ventricular ejection fraction was measured by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 17 individuals at maximal inspiration and expiration and in eight at rest and during the strain phase (phase 2) of the Valsalva manoeuvre. The right ventricular ejection fraction was significantly lower during expiration than during inspiration. There were, however, no significant differences in bolus duration or right ventricular transit time. The Valsalva manoeuvre, in contrast, significantly increased the ejection fraction and also significantly prolonged both the bolus duration and right ventricular transit time. The conformation of the bolus curves during the Valsalva manoeuvre suggested the development of tricuspid regurgitation. These data suggest that relative influences of venous return, pulmonary arterial pressure, pulmonary vascular resistance, and possible functional tricuspid regurgitation vary during inspiration, expiration, and the Valsalva manoeuvre and can affect the right ventricular ejection fraction. Changes in right ventricular function on exercise assessed by first pass radionuclide angiography must be interpreted with caution because maximal respiratory effort may alter the right ventricular ejection fraction independently of ischaemia or other non-ischaemic factors.
Factors other than ischemia may alter right ventricular function both at rest and on exercise. Normal volunteers differ from cardiac patients with normal coronary arteries with regard to their left ventricular response to exercise. This study examined changes in right ventricular function on exercise in 21 normal volunteers and 13 patients with normal coronary arteries, using first-pass radionuclide angiography. There were large ranges of right ventricular ejection fraction in the two groups, both at rest and on exercise. Resting right ventricular ejection fraction was 40.2 +/- 10.6% (mean +/- SD) in the volunteers and 38.6 +/- 9.7% in the patients, p = not significant, and on exercise rose significantly in both groups to 46.1 +/- 9.9% and 45.8 +/- 9.7%, respectively. The difference between the groups was not significant. In both groups some subjects with high resting values showed large decreases in ejection fraction on exercise, and there were significant negative correlations between resting ejection fraction and the change on exercise, r = -0.59 (p less than 0.01) in volunteers, and r = -0.66 (p less than 0.05) in patients. Older volunteers tended to have lower rest and exercise ejection fractions, but there was no difference between normotensive and hypertensive patients in their rest or exercise values. In conclusion, changes in right ventricular function on exercise are similar in normal volunteers and in patients with normal coronary arteries. Some subjects show decreases in right ventricular ejection fraction on exercise which do not appear to be related to ischemia.
The effects of a single oral dose of nisoldipine, 10 mg, were investigated in two groups of patients. Firstly, the effects of nisoldipine on exercise left ventricular function were assessed in 20 patients with chronic stable angina and coronary disease. Secondly, the effects of nisoldipine on the left ventricular response to cold pressor stimulation were examined in 12 patients with normal coronary arteries, who presented with typical ischaemic chest pain and abnormal exercise tests. All studies were performed using first pass radionuclide angiography and the new short half-life radiopharmaceutical, gold-195m. In patients with coronary disease, mean exercise time improved after nisoldipine (P less than 0.01). Both at the identical workload to that before treatment, and at a new peak workload, mean exercise left ventricular ejection fraction (LVEF) improved significantly after nisoldipine (P less than 0.01 and P less than 0.05 vs pretreatment levels, respectively). At the identical workload to that before treatment, 10 of 16 patients, who had initially developed angina, did not develop angina after nisoldipine, and 23 of 46 exercise-induced regional left ventricular abnormalities had normalized. In the patients with normal coronary arteries undergoing cold pressor stimulation, imaging was carried out at rest, and after 1 and 2.5 minutes of cold stimulation, before and one hour after oral nisoldipine. LVEF fell significantly during cold stimulation before nisoldipine administration, with 10 of the 12 patients showing an abnormal response. Nisoldipine did not lead to any attenuation of the heart rate and blood pressure response to cold, but mean LVEF did not fall at any cold pressor stage and only three patients showed an abnormal response.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy and safety of the new cardioselective beta-blocker bisoprolol 5 mg and 10 mg once daily in the treatment of angina pectoris was compared with atenolol 100 mg once daily. 19 patients with coronary artery disease and angina of effort completed a randomised, three-way crossover study which consisted of six-week treatment periods preceeded by a two-week placebo washout. Treadmill exercise stress tests were carried out approximately 24 hours after each dose, at the end of the placebo period and after 2 and 6 weeks of each active treatment period. Patients recorded their angina attack rate and GTN consumption on diary cards. Number of anginal attacks, GTN consumption, resting and exercise systolic blood pressure, heart rate and double product were reduced, and both exercise duration and time to 1 mm ST-segment depression during exercise were increased to a similar extent by all three treatment regimens (P less than 0.01, paired t test). The only differences between the treatments were that the reductions in heart rate, double product and exercise blood pressure tended to be smaller after 6 weeks of bisoprolol 5 mg. Generally, there was no significant difference between the improvements measured at week 2 of each phase and at week 6 (P greater than 0.05, analysis of variance). All three dosage regimens were well tolerated. The data indicate that there is no difference between the safety and efficacy of bisoprolol 10 mg and atenolol 100 mg once daily in the treatment of angina pectoris. In addition, the 10 mg dose of bisoprolol would seem to have only a small advantage over the lower 5 mg once daily dose.
Clinical, electrocardiographic, and scintigraphic data were reviewed from 32 patients (18 men and 14 women) who had syndrome X (chest pain, evidence of ischaemia, and normal coronary arteries without coronary vasospasm). The mean (SD) resting left ventricular ejection fraction, determined by first pass radionuclide angiography was 62.6 (9.2)% and was greater than 50% in all subjects. There was no significant difference between men and women. On exercise, left ventricular ejection fraction decreased significantly to 57.4 (13.0)%. In 17 of 32 subjects there was a fall in left ventricular ejection fraction of greater than 5%, and regional wall motion abnormalities developed in 12 subjects. The fall in left ventricular ejection fraction on exercise was significant in women (from 61.9 (8.5)% at rest to 54.0 (9.8)% on exercise) but not in men (from 63.2 (9.8)% at rest to 60.0 (14.8)% on exercise). Exercise left ventricular ejection fraction fell by greater than 5% in 10 (71%) of 14 women and in seven (39%) of 18 men. Dyskinetic segments developed in eight (57%) of 14 women and only four (22%) of men. Exercise duration in women was significantly shorter than in men (4.1 (1.5) vs 6.6 (2.1) minutes) and was the only one of several clinical and scintigraphic variables that correlated with the change in left ventricular ejection fraction on exercise. In this selected group of subjects with chest pain and angiographically normal coronary arteries, exercise induced left ventricular dysfunction, as shown by a fall in ejection fraction or the development of regional abnormalities, is a common finding. These are more likely to occur in women than men and are associated with a lower exercise capacity. The data suggest that the sex of the patient is important in the interpretation of the non-invasive evaluation of subjects suspected of having syndrome X.
The relation of global and regional right and left ventricular function during the acute phase after a first myocardial infarction was assessed by first pass radionuclide angiography in 20 patients (10 after anterior and 10 after inferior myocardial infarction). The right ventricular ejection fraction did not differ significantly between the groups, but left ventricular ejection fraction was significantly depressed after anterior myocardial infarction. There was evidence of right ventricular dilatation and impaired transit in the group with inferior infarction. Five patients with anterior infarction and six with inferior infarction had abnormal right ventricular ejection fractions. Right ventricular wall motion abnormalities affected the septal wall in the group with anterior infarction and the free wall in the group with inferior infarction. The relation between right and left ventricular ejection fractions was markedly different in the two groups. In the group with anterior infarction there was a significant linear relation between right and left ventricular ejection fraction, whereas in the group with inferior infarction there was not. Thus right ventricular dysfunction commonly occurs after both anterior and inferior myocardial infarction. Right and left ventricular impairment are related after anterior myocardial infarction, but are independent after inferior myocardial infarction. Finally, the different effects of anterior and inferior myocardial infarction on right ventricular function may be explained by differences in septal and free wall involvement.